Am. J. Hum. Genet. 51:585-591, 1992
HLA Heterozygosity Contributes to Susceptibility to Rheumatoid Arthritis Paul Wordsworth,* Kevin D. Pile,* Jonathan D. Buckelyt Jerry S. S. Lanchbury4 Bill Ollier,§ Mark Lathrop, 1 and John 1. Bell* *Institute of Molecular Medicine, Oxford; TDepartment of Preventive Medicine, University of Southern California, Los Angeles; tMolecular Immunogenetics Laboratory, Guy's Hospital, London; §Arthritis and Rheumatism Council Epidemiology Unit, University of Manchester, Manchester; and IlCentre d'Etude du Polymorphisme Humain, Paris
Summary We have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dwl5). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present-Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P < .02) and in those with Felty syndrome (RR 4.2; P < .02). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dwl4 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. We also found four cases with the rare Dw4/Dwl5 genotype (expected
HLA Heterozygosity Contributes to Susceptibility to Rheumatoid Arthritis Paul Wordsworth,* Kevin D. Pile,* Jonathan D. Buckelyt Jerry S. S. Lanchbury4 Bill Ollier,§ Mark Lathrop, 1 and John 1. Bell* *Institute of Molecular Medicine, Oxford; TDepartment of Preventive Medicine, University of Southern California, Los Angeles; tMolecular Immunogenetics Laboratory, Guy's Hospital, London; §Arthritis and Rheumatism Council Epidemiology Unit, University of Manchester, Manchester; and IlCentre d'Etude du Polymorphisme Humain, Paris
Summary We have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dwl5). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present-Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P < .02) and in those with Felty syndrome (RR 4.2; P < .02). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dwl4 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. We also found four cases with the rare Dw4/Dwl5 genotype (expected
